Variably methylated retrotransposons are refractory to a range of environmental perturbations.

Autor: Bertozzi TM; Department of Genetics, University of Cambridge, Cambridge, UK., Becker JL; Department of Genetics, University of Cambridge, Cambridge, UK., Blake GET; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.; Centre for Trophoblast Research, University of Cambridge, Cambridge, UK., Bansal A; Center for Research on Reproduction and Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Australian National University Medical School, John Curtin School of Medical Research, College of Health and Medicine, Australian National University, Canberra, Australian Capital Territory, Australia., Nguyen DK; Department of Cell and Developmental Biology, Perelman School of Medicine, Epigenetics Institute, University of Pennsylvania, Philadelphia, PA, USA., Fernandez-Twinn DS; University of Cambridge Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Wellcome Trust Medical Research Council Institute of Metabolic Science, Cambridge, UK., Ozanne SE; University of Cambridge Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Wellcome Trust Medical Research Council Institute of Metabolic Science, Cambridge, UK., Bartolomei MS; Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Cell and Developmental Biology, Perelman School of Medicine, Epigenetics Institute, University of Pennsylvania, Philadelphia, PA, USA., Simmons RA; Center for Research on Reproduction and Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Watson ED; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.; Centre for Trophoblast Research, University of Cambridge, Cambridge, UK., Ferguson-Smith AC; Department of Genetics, University of Cambridge, Cambridge, UK. afsmith@gen.cam.ac.uk.; Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. afsmith@gen.cam.ac.uk.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2021 Aug; Vol. 53 (8), pp. 1233-1242. Date of Electronic Publication: 2021 Jul 29.
DOI: 10.1038/s41588-021-00898-9
Abstrakt: The agouti viable yellow (A vy ) allele is an insertional mutation in the mouse genome caused by a variably methylated intracisternal A particle (VM-IAP) retrotransposon. A vy expressivity is sensitive to a range of early-life chemical exposures and nutritional interventions, suggesting that environmental perturbations can have long-lasting effects on the methylome. However, the extent to which VM-IAP elements are environmentally labile with phenotypic implications is unknown. Using a recently identified repertoire of VM-IAPs, we assessed the epigenetic effects of different environmental contexts. A longitudinal aging analysis indicated that VM-IAPs are stable across the murine lifespan, with only small increases in DNA methylation detected for a subset of loci. No significant effects were observed after maternal exposure to the endocrine disruptor bisphenol A, an obesogenic diet or methyl donor supplementation. A genetic mouse model of abnormal folate metabolism exhibited shifted VM-IAP methylation levels and altered VM-IAP-associated gene expression, yet these effects are likely largely driven by differential targeting by polymorphic KRAB zinc finger proteins. We conclude that epigenetic variability at retrotransposons is not predictive of environmental susceptibility.
(© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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